Cellular and Molecular Life Sciences

, Volume 76, Issue 2, pp 329–340 | Cite as

A-to-I mRNA editing in fungi: occurrence, function, and evolution

  • Zhuyun Bian
  • Yajia Ni
  • Jin-Rong Xu
  • Huiquan LiuEmail author


A-to-I RNA editing is an important post-transcriptional modification that converts adenosine (A) to inosine (I) in RNA molecules via hydrolytic deamination. Although editing of mRNAs catalyzed by adenosine deaminases acting on RNA (ADARs) is an evolutionarily conserved mechanism in metazoans, organisms outside the animal kingdom lacking ADAR orthologs were thought to lack A-to-I mRNA editing. However, recent discoveries of genome-wide A-to-I mRNA editing during the sexual stage of the wheat scab fungus Fusarium graminearum, model filamentous fungus Neurospora crassa, Sordaria macrospora, and an early diverging filamentous ascomycete Pyronema confluens indicated that A-to-I mRNA editing is likely an evolutionarily conserved feature in filamentous ascomycetes. More importantly, A-to-I mRNA editing has been demonstrated to play crucial roles in different sexual developmental processes and display distinct tissue- or development-specific regulation. Contrary to that in animals, the majority of fungal RNA editing events are non-synonymous editing, which were shown to be generally advantageous and favored by positive selection. Many non-synonymous editing sites are conserved among different fungi and have potential functional and evolutionary importance. Here, we review the recent findings about the occurrence, regulation, function, and evolution of A-to-I mRNA editing in fungi.


RNA modification Deamination Adenosine Inosine Sexual reproduction Fusarium graminearum Neurospora crassa Epigenetic Adaptation ADAR ADAT Non-synonymous editing 



We thank Ruonan Hei for assistance in preparing the illustrations and Drs. Cong Jiang, Qinhu Wang, and Chenfang Wang for fruitful discussions. We also thank Dr. Larry Dunkle at Purdue University for language editing the manuscript. This work was supported by grants from the National Science Fund for Excellent Young Scholars (Grant 31622045) and the National Youth Talent Support Program (Z111021802) to HL, and grants from the US Wheat Barley Scab Initiative and National Science Foundation to JX.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.


  1. 1.
    Benne R, Van den Burg J, Brakenhoff JP, Sloof P, Van Boom JH, Tromp MC (1986) Major transcript of the frameshifted coxII gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Cell 46:819–826CrossRefGoogle Scholar
  2. 2.
    Aphasizhev R, Aphasizheva I (2014) Mitochondrial RNA editing in trypanosomes: small RNAs in control. Biochimie 100:125–131CrossRefGoogle Scholar
  3. 3.
    Knoop V (2011) When you can’t trust the DNA: RNA editing changes transcript sequences. Cell Mol Life Sci 68:567–586CrossRefGoogle Scholar
  4. 4.
    Chateigner-Boutin AL, Small I (2011) Organellar RNA editing. Wiley Interdiscip Rev RNA 2:493–506CrossRefGoogle Scholar
  5. 5.
    Knisbacher BA, Gerber D, Levanon EY (2016) DNA editing by APOBECs: a genomic preserver and transformer. Trends Genet 32:16–28CrossRefGoogle Scholar
  6. 6.
    Salter JD, Bennett RP, Smith HC (2016) The APOBEC protein family: united by structure, divergent in function. Trends Biochem Sci 41:578–594CrossRefGoogle Scholar
  7. 7.
    Sun T, Bentolila S, Hanson MR (2016) The unexpected diversity of plant organelle RNA editosomes. Trends Plant Sci 21:962–973CrossRefGoogle Scholar
  8. 8.
    Nishikura K (2010) Functions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem 79:321–349CrossRefGoogle Scholar
  9. 9.
    Sommer B, Kohler M, Sprengel R, Seeburg PH (1991) RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67:11–19CrossRefGoogle Scholar
  10. 10.
    Torres AG, Pineyro D, Filonava L, Stracker TH, Batlle E, Ribas de Pouplana L (2014) A-to-I editing on tRNAs: biochemical, biological and evolutionary implications. FEBS Lett 588:4279–4286CrossRefGoogle Scholar
  11. 11.
    Holley RW, Everett GA, Madison JT, Zamir A (1965) Nucleotide sequences in the yeast alanine transfer ribonucleic acid. J Biol Chem 240:2122–2128Google Scholar
  12. 12.
    Gerber A, Grosjean H, Melcher T, Keller W (1998) Tad1p, a yeast tRNA-specific adenosine deaminase, is related to the mammalian pre-mRNA editing enzymes ADAR1 and ADAR2. EMBO J 17:4780–4789CrossRefGoogle Scholar
  13. 13.
    Gerber AP, Keller W (1999) An adenosine deaminase that generates inosine at the wobble position of tRNAs. Science 286:1146–1149CrossRefGoogle Scholar
  14. 14.
    Grice LF, Degnan BM (2015) The origin of the ADAR gene family and animal RNA editing. BMC Evol Biol 15:4CrossRefGoogle Scholar
  15. 15.
    Savva YA, Rieder LE, Reenan RA (2012) The ADAR protein family. Genome Biol 13:252CrossRefGoogle Scholar
  16. 16.
    Gerber AP, Keller W (2001) RNA editing by base deamination: more enzymes, more targets, new mysteries. Trends Biochem Sci 26:376–384CrossRefGoogle Scholar
  17. 17.
    Tan MH et al (2017) Dynamic landscape and regulation of RNA editing in mammals. Nature 550:249–254CrossRefGoogle Scholar
  18. 18.
    Jin Y, Zhang W, Li Q (2009) Origins and evolution of ADAR-mediated RNA editing. IUBMB Life 61:572–578CrossRefGoogle Scholar
  19. 19.
    Keegan LP, McGurk L, Palavicini JP, Brindle J, Paro S, Li X, Rosenthal JJ, O’Connell MA (2011) Functional conservation in human and Drosophila of Metazoan ADAR2 involved in RNA editing: loss of ADAR1 in insects. Nucleic Acids Res 39:7249–7262CrossRefGoogle Scholar
  20. 20.
    Bar-Yaacov D, Mordret E, Towers R, Biniashvili T, Soyris C, Schwartz S, Dahan O, Pilpel Y (2017) RNA editing in bacteria recodes multiple proteins and regulates an evolutionarily conserved toxin–antitoxin system. Genome Res 27:1696–1703CrossRefGoogle Scholar
  21. 21.
    Liu H, Li Y, Chen D, Qi Z, Wang Q, Wang J, Jiang C, Xu JR (2017) A-to-I RNA editing is developmentally regulated and generally adaptive for sexual reproduction in Neurospora crassa. Proc Natl Acad Sci USA 114:E7756–E7765CrossRefGoogle Scholar
  22. 22.
    Teichert I, Dahlmann TA, Kuck U, Nowrousian M (2017) RNA editing during sexual development occurs in distantly related filamentous ascomycetes. Genome Biol Evol 9:855–868CrossRefGoogle Scholar
  23. 23.
    Cao S, He Y, Hao C, Xu Y, Zhang H, Wang C, Liu H, Xu JR (2017) RNA editing of the AMD1 gene is important for ascus maturation and ascospore discharge in Fusarium graminearum. Sci Rep 7:4617CrossRefGoogle Scholar
  24. 24.
    Liu H et al (2016) Genome-wide A-to-I RNA editing in fungi independent of ADAR enzymes. Genome Res 26:499–509CrossRefGoogle Scholar
  25. 25.
    Wang Q, Jiang C, Liu H, Xu J-R (2016) ADAR-independent A-to-I RNA editing is generally adaptive for sexual reproduction in fungi. bioRxiv: 059725Google Scholar
  26. 26.
    Hung LY, Chen YJ, Mai TL, Chen CY, Yang MY, Chiang TW, Wang YD, Chuang TJ (2018) An evolutionary landscape of A-to-I RNA editome across metazoan species. Genome Biol Evol 10:521–537CrossRefGoogle Scholar
  27. 27.
    Porath HT, Knisbacher BA, Eisenberg E, Levanon EY (2017) Massive A-to-I RNA editing is common across the Metazoa and correlates with dsRNA abundance. Genome Biol 18:185CrossRefGoogle Scholar
  28. 28.
    Eggington JM, Greene T, Bass BL (2011) Predicting sites of ADAR editing in double-stranded RNA. Nat Commun 2:319CrossRefGoogle Scholar
  29. 29.
    Zhang R, Deng P, Jacobson D, Li JB (2017) Evolutionary analysis reveals regulatory and functional landscape of coding and non-coding RNA editing. PLoS Genet 13:e1006563CrossRefGoogle Scholar
  30. 30.
    Deffit SN, Hundley HA (2016) To edit or not to edit: regulation of ADAR editing specificity and efficiency. Wiley Interdiscip Rev RNA 7:113–127CrossRefGoogle Scholar
  31. 31.
    Wahlstedt H, Ohman M (2011) Site-selective versus promiscuous A-to-I editing. Wiley Interdiscip Rev RNA 2:761–771CrossRefGoogle Scholar
  32. 32.
    Pöggeler S, Nowrousian M, Teichert I, Beier A, Kück U (2018) Fruiting-body development in ascomycetes. In: Physiology and genetics, 2nd edn. Springer, Berlin, pp 1–56Google Scholar
  33. 33.
    Walkley CR, Li JB (2017) Rewriting the transcriptome: adenosine-to-inosine RNA editing by ADARs. Genome Biol 18:205CrossRefGoogle Scholar
  34. 34.
    Picardi E, Manzari C, Mastropasqua F, Aiello I, D’Erchia AM, Pesole G (2015) Profiling RNA editing in human tissues: towards the inosinome Atlas. Sci Rep 5:14941CrossRefGoogle Scholar
  35. 35.
    Liscovitch-Brauer N et al (2017) Trade-off between transcriptome plasticity and genome evolution in cephalopods. Cell 169(191–202):e11Google Scholar
  36. 36.
    Ramaswami G, Li JB (2014) RADAR: a rigorously annotated database of A-to-I RNA editing. Nucleic Acids Res 42:D109–D113CrossRefGoogle Scholar
  37. 37.
    Zhao HQ et al (2015) Profiling the RNA editomes of wild-type C. elegans and ADAR mutants. Genome Res 25:66–75CrossRefGoogle Scholar
  38. 38.
    St Laurent G et al (2013) Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in Drosophila. Nat Struct Mol Biol 20:1333–1339CrossRefGoogle Scholar
  39. 39.
    Palavicini JP, O’Connell MA, Rosenthal JJ (2009) An extra double-stranded RNA binding domain confers high activity to a squid RNA editing enzyme. RNA 15:1208–1218CrossRefGoogle Scholar
  40. 40.
    Xu G, Zhang J (2014) Human coding RNA editing is generally nonadaptive. Proc Natl Acad Sci USA 111:3769–3774CrossRefGoogle Scholar
  41. 41.
    Duan Y, Dou S, Luo S, Zhang H, Lu J (2017) Adaptation of A-to-I RNA editing in Drosophila. PLoS Genet 13:e1006648CrossRefGoogle Scholar
  42. 42.
    Yu Y, Zhou H, Kong Y, Pan B, Chen L, Wang H, Hao P, Li X (2016) The landscape of A-to-I RNA editome is shaped by both positive and purifying selection. PLoS Genet 12:e1006191CrossRefGoogle Scholar
  43. 43.
    Alon S, Garrett SC, Levanon EY, Olson S, Graveley BR, Rosenthal JJ, Eisenberg E (2015) The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing. Elife 4:e05198CrossRefGoogle Scholar
  44. 44.
    Gommans WM, Mullen SP, Maas S (2009) RNA editing: a driving force for adaptive evolution? BioEssays 31:1137–1145CrossRefGoogle Scholar
  45. 45.
    Garrett S, Rosenthal JJ (2012) RNA editing underlies temperature adaptation in K+ channels from polar octopuses. Science 335:848–851CrossRefGoogle Scholar
  46. 46.
    Buchumenski I, Bartok O, Ashwal-Fluss R, Pandey V, Porath HT, Levanon EY, Kadener S (2017) Dynamic hyper-editing underlies temperature adaptation in Drosophila. PLoS Genet 13:e1006931CrossRefGoogle Scholar
  47. 47.
    Rieder LE, Savva YA, Reyna MA, Chang YJ, Dorsky JS, Rezaei A, Reenan RA (2015) Dynamic response of RNA editing to temperature in Drosophila. BMC Biol 13:1CrossRefGoogle Scholar
  48. 48.
    Palladino MJ, Keegan LP, O’Connell MA, Reenan RA (2000) A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell 102:437–449CrossRefGoogle Scholar
  49. 49.
    Belotserkovskaya R, Sterner DE, Deng M, Sayre MH, Lieberman PM, Berger SL (2000) Inhibition of TATA-binding protein function by SAGA subunits Spt3 and Spt8 at Gcn4-activated promoters. Mol Cell Biol 20:634–647CrossRefGoogle Scholar
  50. 50.
    Black DL (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem 72:291–336CrossRefGoogle Scholar
  51. 51.
    Porath HT, Carmi S, Levanon EY (2014) A genome-wide map of hyper-edited RNA reveals numerous new sites. Nat Commun 5:4726CrossRefGoogle Scholar
  52. 52.
    Klauer AA, van Hoof A (2012) Degradation of mRNAs that lack a stop codon: a decade of nonstop progress. Wiley Interdiscip Rev RNA 3:649–660CrossRefGoogle Scholar
  53. 53.
    Ito-Harashima S, Kuroha K, Tatematsu T, Inada T (2007) Translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization by proteasome in yeast. Genes Dev 21:519–524CrossRefGoogle Scholar
  54. 54.
    Arribere JA, Cenik ES, Jain N, Hess GT, Lee CH, Bassik MC, Fire AZ (2016) Translation readthrough mitigation. Nature 534:719–723CrossRefGoogle Scholar
  55. 55.
    Shibata N et al (2015) Degradation of stop codon read-through mutant proteins via the ubiquitin-proteasome system causes hereditary disorders. J Biol Chem 290:28428–28437CrossRefGoogle Scholar
  56. 56.
    Steneberg P, Samakovlis C (2001) A novel stop codon readthrough mechanism produces functional Headcase protein in Drosophila trachea. EMBO Rep 2:593–597CrossRefGoogle Scholar
  57. 57.
    Freitag J, Ast J, Bolker M (2012) Cryptic peroxisomal targeting via alternative splicing and stop codon read-through in fungi. Nature 485:522–525CrossRefGoogle Scholar
  58. 58.
    Schueren F, Thoms S (2016) Functional translational readthrough: a systems biology perspective. PLoS Genet 12:e1006196CrossRefGoogle Scholar
  59. 59.
    Dunn JG, Foo CK, Belletier NG, Gavis ER, Weissman JS (2013) Ribosome profiling reveals pervasive and regulated stop codon readthrough in Drosophila melanogaster. Elife 2:e01179CrossRefGoogle Scholar
  60. 60.
    Schueren F, Lingner T, George R, Hofhuis J, Dickel C, Gartner J, Thoms S (2014) Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals. Elife 3:e03640CrossRefGoogle Scholar
  61. 61.
    Eswarappa SM et al (2014) Programmed translational readthrough generates antiangiogenic VEGF-Ax. Cell 157:1605–1618CrossRefGoogle Scholar
  62. 62.
    Xu G, Zhang J (2015) In search of beneficial coding RNA editing. Mol Biol Evol 32:536–541CrossRefGoogle Scholar
  63. 63.
    Pinto Y, Cohen HY, Levanon EY (2014) Mammalian conserved ADAR targets comprise only a small fragment of the human editosome. Genome Biol 15:R5CrossRefGoogle Scholar
  64. 64.
    Kroger B, Vinther J, Fuchs D (2011) Cephalopod origin and evolution: a congruent picture emerging from fossils, development and molecules: extant cephalopods are younger than previously realised and were under major selection to become agile, shell-less predators. BioEssays 33:602–613CrossRefGoogle Scholar
  65. 65.
    Aramayo R, Selker EU (2013) Neurospora crassa, a model system for epigenetics research. Cold Spring Harb Perspect Biol 5:a017921CrossRefGoogle Scholar
  66. 66.
    Smith KM, Phatale PA, Bredeweg EL, Connolly LR, Pomraning KR, Freitag M (2012) Epigenetics of filamentous fungi Epigenetic regulation and epigenomics. Wiley, Hoboken, pp 1063–1107 (Curr Top Encycl Mol Cell Biol) Google Scholar
  67. 67.
    Wang C, Xu JR, Liu H (2016) A-to-I RNA editing independent of ADARs in filamentous fungi. RNA Biol 13:940–945CrossRefGoogle Scholar
  68. 68.
    Koutelou E, Hirsch CL, Dent SY (2010) Multiple faces of the SAGA complex. Curr Opin Cell Biol 22:374–382CrossRefGoogle Scholar
  69. 69.
    Freitag M, Williams RL, Kothe GO, Selker EU (2002) A cytosine methyltransferase homologue is essential for repeat-induced point mutation in Neurospora crassa. Proc Natl Acad Sci USA 99:8802–8807CrossRefGoogle Scholar
  70. 70.
    Pomraning KR, Connolly LR, Whalen JP, Smith KM, Freitag M (2013) Repeat-induced point mutation, DNA methylation and heterochromatin in Gibberella zeae (anamorph: Fusarium graminearum). In: Fusarium: genomics, molecular and cellular biology, 2nd edn. Horizon Scientific Press, ‎Poole, p 93Google Scholar
  71. 71.
    Schmitt I (2011) 8 Fruiting body evolution in the ascomycota: a molecular perspective integrating lichenized and non-lichenized groups. In: Evolution of fungi and fungal-like organisms, 2nd edn. Springer, Berlin, pp 187–204Google Scholar
  72. 72.
    Rodenburg SYA, Terhem RB, Veloso J, Stassen JHM, van Kan JAL (2018) Functional analysis of mating type genes and transcriptome analysis during fruiting body development of Botrytis cinerea. MBio 9:e01939-17CrossRefGoogle Scholar
  73. 73.
    Wang IX, Grunseich C, Chung YG, Kwak H, Ramrattan G, Zhu Z, Cheung VG (2016) RNA-DNA sequence differences in Saccharomyces cerevisiae. Genome Res 26:1544–1554CrossRefGoogle Scholar
  74. 74.
    Wu B et al (2018) Substrate-specific differential gene expression and RNA editing in the Brown Rot Fungus Fomitopsis pinicola. Appl Environ Microbiol 84(16). pii: e00991–18.
  75. 75.
    Zhu Y, Luo H, Zhang X, Song J, Sun C, Ji A, Xu J, Chen S (2014) Abundant and selective RNA-editing events in the medicinal mushroom Ganoderma lucidum. Genetics 196:1047–1057CrossRefGoogle Scholar
  76. 76.
    Gray MW (2012) Evolutionary origin of RNA editing. Biochemistry 51:5235–5242CrossRefGoogle Scholar
  77. 77.
    Covello PS, Gray MW (1993) On the evolution of RNA editing. Trends Genet 9:265–268CrossRefGoogle Scholar
  78. 78.
    Hadany L, Otto SP (2007) The evolution of condition-dependent sex in the face of high costs. Genetics 176:1713–1727CrossRefGoogle Scholar
  79. 79.
    Wallen RM, Perlin MH (2018) An overview of the function and maintenance of sexual reproduction in dikaryotic fungi. Front Microbiol 9:503CrossRefGoogle Scholar
  80. 80.
    de Visser JAGM, Elena SF (2007) The evolution of sex: empirical insights into the roles of epistasis and drift. Nat Rev Genet 8:139–149CrossRefGoogle Scholar
  81. 81.
    Goddard MR, Godfray HC, Burt A (2005) Sex increases the efficacy of natural selection in experimental yeast populations. Nature 434:636–640CrossRefGoogle Scholar
  82. 82.
    Burt A (2000) Perspective: sex, recombination, and the efficacy of selection—was Weismann right? Evolution 54:337–351Google Scholar
  83. 83.
    Koltin Y, Stamberg J, Ronen R (1975) Meiosis as a source of spontaneous mutations in Schizophyllum commune. Mutat Res Fund Mol Mech Mutagen 27:319–325CrossRefGoogle Scholar
  84. 84.
    Rattray A, Santoyo G, Shafer B, Strathern JN (2015) Elevated mutation rate during meiosis in Saccharomyces cerevisiae. PLoS Genet 11:e1004910CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Crop Stress Biology for Arid Areas, Purdue-NWAFU Joint Research Center, College of Plant ProtectionNorthwest A&F UniversityYanglingChina
  2. 2.Department of Botany and Plant PathologyPurdue UniversityWest LafayetteUSA

Personalised recommendations